Intensified androgen deprivation therapy (ADT) with apalutamide (APA) with or without abiraterone acetate plus prednisone (AAP), administered for a finite treatment duration of 52 weeks prolonged PSA progression-free survival (PFS) in men with high-risk biochemically-relapsed prostate cancer, according to new data presented at the American Society of Clinical Oncology’s 2023 Genitourinary Cancers Symposium in San Francisco, California

In the phase 3 PRESTO study, investigators found a Gleason score of 9 or 10 at diagnosis was associated with shorter median PSA PFS compared with a Gleason score of 8 and Gleason score of 6 to 7 (21.9 vs 31.1 and 25.2 months). They observed a shorter median PSA PFS for men with Gleason 9 or 10 cancer in each treatment arm.

Serum PSA and PSA doubling time at study entry, time from prior radical prostatectomy (RP), and prior radiation were found not to be associated with PSA PFS in the overall study cohort or in individual study arms.

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“The findings are consistent with other phase 3 studies of intensified hormone therapy reported in the metastatic castration sensitive setting, which have also consistently demonstrated an improvement in efficacy outcomes compared to ADT alone,” said study investigator Rahul Aggarwal, MD, Associate Professor of Medicine and Associate Director for Clinical Research at the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco.

The study included 503 men with BRPC after RP, a PSA doubling time of 9 months or less, and no distant metastases on conventional imaging. Investigators randomly assigned patients to receive ADT alone (166 men; control group), ADT + APA (168 men) or ADT + APA + AAP (169 men). The 3 treatment arms were well balanced in terms of baseline characteristics, including Gleason sum at diagnosis, serum PSA, and PSADT at study entry. Investigators stratified men according PSADT (less than 3 vs 3-9 months).

Both experimental arms experienced significantly prolonged PSA PFS compared with the control group. The median PFS was 24.9 and 26.0 months for the ADT + APA arm and ADT + APA + AAP arm, respectively, compared with 20.3 months for the ADT-only arm. Compared with the control group, those in the ADT + APA arm and the ADT + APA + AAP arm had a 48% and 52% lower risk for PSA progression.

“I do not think the results presented thus far are sufficient to change clinical practice for all men with biochemically relapsed disease,” said Dr Aggarwal, who presented study findings. “However, I do think the combination of ADT plus apalutamide should be discussed on an individual basis for a subset of patients.”

These patients include men with very high-risk disease and short PSA doubling times, without significant co-morbidities, he said. The goal of this approach is to prolong PFS and potentially lengthen the treatment-free interval as part of an intermittent therapeutic framework.

“The study was powered to detect a difference in PSA progression-free survival, and that is what we observed at the first interim analysis,” Dr Aggarwal said. “Follow-up is ongoing to determine the impact of ADT treatment intensification on longer term outcomes, including time to re-initiation of systemic therapy, metastasis-free survival, and time to castration resistance.”

Teja Ganta, MD, a clinical fellow in the Division of Hematology and Medical Oncology in the Icahn School of Medicine at Mount Sinai in New York City, said many men continue to struggle with contextualizing their treatment options for biochemically recurrent disease. “This study provides additional data that the medications currently used for prostate cancer can be intensified and potentially translate to measurable benefits,” Dr Ganta said. “The findings are clinically relevant and ought to be discussed with patients. However, combination regimens can have additional adverse events and financial toxicity, which are important for patients to know when weighing their treatment options.”

Matthew Zibelman, MD, Associate Professor, Department of Hematology/Oncology, Fox Chase Cancer Center in Philadelphia, Pennsylvania, said there is great unmet need when it comes to treating men with BRPC, for whom no clear standard of care exists. These men are asymptomatic from their disease, so any treatment in this setting must have negligible short-term and long-term toxicity and/or significantly improve their long-term survival and quality of life. “While this study represents an important albeit unsurprising early signal of activity, how these patients’ survival is affected with longer follow-up is critical,” Dr Zibelman said.

These current findings should not alter current practice, Dr Zibelman noted. Future analysis of this trial and additional studies need to address longer term outcomes such as overall survival, while sub-group analyses broken down by PSA doubling time at study entry may help stratify patients most likely to benefit. “Additional studies utilizing modern PET-based imaging techniques and other biomarkers may also help better define those patients most likely to benefit from, or safely defer early systemic treatment,” he said.

Disclosure: Janssen Pharmaceuticals provided research funding for the study.


Aggarwal RR, Heller G, Hillman DW, et al. Baseline characteristics associated with PSA progression-free survival in patients with high-risk biochemically relapsed prostate cancer: Results from the phase 3 PRESTO study. Presented at: ASCO GU 2023, San Francisco, California, February 16-18. Abstract 208.